Project Summary Gastric contractions are initiated and coordinated by an underlying bioelectrical activity termed slow waves (SWs). Aberrant SW patterns (dysrhythmias) have been associated with gastric dysmotility in several significant gastric disorders, notably gastroparesis (GP) and functional dyspepsia. There are also well- documented associations between GP and damage to the vagus nerve that are common in people with diabetes. Gastric pacing and vagus nerve stimulation have been proposed as treatment modalities for gastric dysrhythmia. However, the pathophysiological roles of electrical dysrhythmias and neural mechanisms in gastric motility disorders, and the role and therapeutic potential of the vagus and gastric electrical stimulation remain weakly defined. This is mainly due to the lack of technologies that can reveal the mechanisms of action. Electroneurogram (ENG) signals obtained through cuff electrodes from the peripheral nerves have been shown to provide valuable information regarding operation of afferent and efferent nerves. Compared to microelectrodes, cuff electrodes are minimally invasive and provide stable recordings long-term. These signals have been used to study neuromuscular, cardiovascular, gastrointestinal, sympathetic and parasympathetic systems. The ENG signal is most informative when it can be associated with the function of the end organ. When studying conscious freely-behaving subjects, this requires implantable devices that can simultaneously acquire ENG and associated organ functions. To fully understand the underlying mechanisms of action of gastric pacing and neuromodulation therapies for functional motility disorders, a tool that can map and monitor?in high resolution?the coordinated activity of gastric SWs and ENG signals from peripheral nerves such as vagal branches innervating the stomach in real time would be invaluable. Gastric SWs directly recorded from the stomach serosa provide the only reliable and descriptive source of data on spatial dysrhythmic patterns. However, a key limitation is that wires traverse the abdominal wall or a natural orifice, posing risks of discomfort, dislodgement, or infection. We propose to develop and validate, in a porcine model, a Wireless Implantable Neuro- Gastroenterology System (WINGS) that can simultaneously acquire SWs and compound action potentials from the gastric peripheral nerves and map these signals in high resolution. The system consists of an implantable system-on-chip to condition and wirelessly transmit the signals, a wearable unit to wirelessly recharge the implant and relay the signals, and a receiver connected to a computer to display, store, and process the data. With its dual capability to monitor ENGs and SWs, WINGS can be implanted laparoscopically or endoscopically via a single minimally invasive procedure. Because the two types of signals will be acquired by one device, their precise timing will be known, and no synchronization will be required.